1. Field
The present invention relates generally to programming of biomolecular self-assembly pathways and related methods and constructs.
2. Background
Molecular self-assembly, a fundamental process underlying the replication and regulation of biological systems, has emerged as an important engineering paradigm for nanotechnology. For example, molecular nanotechnology uses positionally-controlled mechanosynthesis guided by molecular systems. Molecular nanotechnology involves combining physical principles demonstrated by the molecular machinery of life, chemistry, and other nanotechnologies with the systems engineering principles found in modern macroscale factories.
In biological systems, self-assembling and disassembling complexes of proteins and nucleic acids bound to a variety of ligands perform intricate and diverse dynamic functions. Attempts to rationally encode structure and function into synthetic amino and nucleic acid sequences have largely focused on engineering molecules that self-assemble into prescribed target structures without explicit concern for transient system dynamics. See, Butterfoss, G. L. & Kuhlman, Annu. Rev. Bioph. Biom. 35, 49-65 (2006); Seeman, N. C., Nature 421, 427-431(2003).
Current protocols for self-assembling synthetic DNA nanostructures often rely on annealing procedures to bring interacting DNA strands to equilibrium on the free energy landscape. Winfree et al., Nature 394, 539-544 (1998); Shih et al., Nature 427, 618-621 (2004); Rothemund, Nature 440, 297-302 (2006). Self-assembly in biology proceeds isothermally and assembly kinetics are often controlled by catalysts. To date, synthetic DNA catalysts have been used to control the kinetics of the formation of DNA duplex structures. Turberfield, A. J. et al., Phys. Rev. Lett. 90, 118102 (2003); Bois, J. S. et al., Nucleic Acids Res. 33, 4090-4095 (2005); Green, S. J. et al., Biophys. J. 91, 2966-2975 (2006); Seelig, G. et al., J. Am. Chem. Soc. 128, 12211-12220 (2006). However, until now, it has remained challenging to mimic nature's ability to encode dynamic function in the design space of biomolecules. Thus, there is a need for systems that are designed to autonomously perform dynamic functions.